Certain new aurones having an oxypropanolamine group at the 6-position and their use for antagonizing the spasmogenic activity of leukotriene C.sub.4 (LTC.sub.4) in animals are described. In particular, the compounds of the invention are expected to be useful for preventing and treating certain obstructive airways diseases, notably allergic bronchial asthma.
The leukotrienes (LT's) have been identified as the major constituents of SRS-A (slow reacting substance of anaphylaxis). Pharmacological studies indicated that LTC.sub.4, LTD.sub.4, and LTE.sub.4 can induce prolonged contraction of smooth muscle in vitro and in vivo, and are important mediators in the triggering of alleric bronchial asthma.
A widely studied specific antagonist of SRS-A is sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl -4H-1-benzopyran-2-carboxylate (FPL 55712) (Agents and Actions, 9, 133 [1979]).
Aurone derivatives wherein either or both phenyl moiety is unsubstituted or substituted with halogen, alkyl, alkoxy, cycloalkyl, phenyl, NH.sub.2, cyano, OH, NO.sub.2, alkenyl, CO.sub.2 H, 5-tetrazolyl or CH:CHCO.sub.2 H were claimed to be useful in the treatment of allergies (Romanian Description of the Invention No. 79,685, published July 30, 1982). These compounds do not have the oxypropanolamine side chains which are attached to compounds in the present invention.
Aurone derivatives in which either or both phenyl moiety is unsubstituted or substituted with halogen, alkyl, alkoxy, cycloalkyl, optionally substituted phenyl, haloalkyl, acylamino, carbamoyl, mono- or di-alkylcarbamoyl, amino, mono- or di(alkyl)amino, cyano, hydroxy, nitro, alkenyl, 5-tetrazoyl or carboxyvinyl have been claimed to have antiinflammatory activity (UK Patent Application No. GB 2 131 688 A, published June 27, 1984).